Brain Injury

TBI (traumatic brain injury) is a  
traumatic insult to the brain from an
external mechanical force, such as a
car accident, a fall or an explosion.
The injury can lead to permanent or
temporary impairments of cognitive,
physical and psychosocial functions
with an associated diminished or
altered state of consciousness. An
estimated 1.7 million Americans per
year suffer a TBI, resulting in 52,000
deaths, 275,000 hospitalizations and
80,000 cases of long-term disability.
It is also the leading cause of death
and disability in children and young
adults worldwide, TBI is involved in
nearly half of all trauma deaths. Traffic
accidents account for 40-50 percent of
the hospitalizations related to the
The annual incidence of TBI is higher
than breast cancer and HIV/AIDS
combined, yet it is largely ignored.

The ProTECT study will determine if
intravenous (IV) progesterone (started
within 4 hours of injury and given for a
total of 96 hours), is more effective
than placebo for treating victims of
moderate to severe acute traumatic
brain injury.
Trial no: NCT00822900
The new three-to-six-year trial, which is
known as proTECT III  will be led by
David Wright, MD, associate professor
of emergency medicine at Emory
University School of Medicine. Atlanta’s
Grady Memorial Hospital has been
designated the lead center.

The possible introduction of
progesterone as treatment for brain
injured patients will be most welcome
by the medical community, as there
have been no effective treatments for
such injuries.

Progesterone, a hormone that has a
role in female fertility, it also seem to
protect brain cells  in  brain injured

This large-scale trial, which will involve
hospitals in 15 states, was prompted
by findings from several previous
studies, including a recent small study
in which investigators found that
administering progesterone soon after
a brain injury reduced the death rate
by 50 percent and improved the
patients’ ability to recover.

Another earlier study conducted at
Zhejiang University in China two years
ago found that patients with serious
brain injuries who were given
progesterone were more likely to
survive than those who received a
placebo. Among the patients who
survived, those who had received
progesterone had made a good
recovery at six months after treatment
(58% of patients) compared with those
who had received placebo (42% of

In the new trial, hospitals will randomly
assign 1,140 patients who arrive for
emergency care within 11 hours of
their brain injury to receive either three
days of infusion treatments with
progesterone or placebo. Because it
appears the infusions are most
effective if given within 11 hours of a
patient’s injury, it may not always be
possible to obtain consent from next of
kin for a patient to take part in the trial.
The Food and Drug Administration has
drawn up special rules to allow trials
that involve emergency medical
treatments to proceed without consent.

Another trial called  SyNAPSe  Phase
3  will study if giving intravenous (i.v.)
progesterone within 8 hours of the
injury for a total of 120 hours to severe
traumatic brain injury patients
improves their recovery.
Trial no: NCT01143064 and it is
conducted by  BHR Pharma, LLC.
"This drug has the potential to help a
gravely ill population that includes car
crash and battlefield injuries and we
could not be more pleased to initiate
this important trial," said Tom
MacAllister, J.D., Ph.D., BHR president
and CEO. "The annual incidence of
TBI is higher than breast cancer and
HIV/AIDS combined, yet it is largely
ignored. We are proud to lead the
efforts to make a difference for these
patients and their families."

Currently, the lack of water solubility
limits delivery of progesterone, in that
the hormone must be prepared hours
ahead and cannot be kept at room
temperature. Small chemical
modifications may allow similar
compounds with the same effects as
progesterone to be given to patients
closer to the time of injury.

Another idea is that  adding vitamin D
to progesterone enhances the
hormone’s effectiveness when applied
to neurons under stress in the
laboratory. Like progesterone, vitamin
D is a steroid hormone that is
inexpensive, has good safety
properties and acts on many different
biochemical pathways.
BHR Pharma is a wholly owned
subsidiary of Besins Healthcare SA,
which markets healthcare products in
93 countries.